Exploring Aromatic Donor-Acceptor Interactions in Water

探索水中芳香族供体-受体相互作用

• 批准号: 7013136
• 负责人: BRENT L IVERSON
• 金额: $ 24.95万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-02 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7013136
• 关键词: X ray crystallography; carbopolycyclic compound; chemical reaction; covalent bond; enzyme linked immunosorbent assay; flow cytometry; high performance liquid chromatography; naphthalenes; nuclear magnetic resonance spectroscopy; oxidizing agents; protein protein interaction; protein structure; proteomics; reducing agents; water

DESCRIPTION (provided by applicant): But can we make it work in water? Chemists are now exploring the design of molecular architectures that extend beyond covalent bonding. Taking inspiration from Nature, molecules that fold or self-assemble are being designed from first principles. Creating molecular systems that fold and assemble in water is currently a major challenge, although once created, such systems will be able to interact with biological structures and molecules in unprecedented ways. Our early foldamer studies verified that aromatic donor-acceptor interactions can be used as a remarkably strong stabilizing interaction in water, producing folded, stacked structures (Lokey and Iverson, Nature, 1995, 375, 303-5.) called aedamers. More recently, we have made the exciting discovery that chains of electron rich aromatic units will specifically recognize a complementary chain of electron deficient aromatic units in aqueous solution to form a stable duplex (Gabriel and Iverson, J. of the Am. Chem. Soc., 2002, 124, 15174-15175.). The first two specific aims of this proposal describe the creation and characterization of novel folding and assembling molecular systems that in water exploit the stabilizing and recognition abilities of the electron rich 1,5-dialkoxynaphthalene (DAN) and the electron deficient 1,4,5,8-naphthalene tetracarboxylic diimide (NDI) aromatic moieties. The last three specific aims take the next critical step and probe different interaction strategies with biological molecules. Spanning the range from basic science to practical application, we will 1) investigate an entirely new aedamer folding topology analogous to nucleic acid hairpins, 2) use the recognition ability of the DAN-NDI interaction to produce large molecular assemblies from smaller folding pieces, 3) investigate the utility of DAN-NDI interactions as a stabilizing force in a protein hydrophobic core, 4) create next-generation threading DNA poly-intercalators based on structures derived from NMR analysis of our NDI-based oligomers, and 5) use phage display to isolate a peptide with high affinity and specificity for binding a chain of NDI residues for potential use in biomedical and biotechnological applications.

描述（由申请人提供）：但是我们可以在水中工作吗？化学家现在正在探索超越共价键合的分子体系结构的设计。从自然中汲取灵感，折叠或自我组装的分子是根据第一原则设计的。目前，创建在水中折叠和聚集的分子系统是一个主要挑战，尽管一旦创建，这种系统将能够以前所未有的方式与生物结构和分子相互作用。我们的早期折叠剂研究验证了芳族供体 - 受体相互作用可以用作水中非常强大的稳定相互作用，从而产生折叠的，堆叠的结构（Lokey and Iverson，Nature，1995，375，375，303-5。）。最近，我们提出了一个令人兴奋的发现，即富含电子芳香族单元的链条将特别识别水溶液中电子缺乏的芳香族单元的互补链，形成稳定的双链体（Gabriel and Iverson，Am。Chem。Chec。的J. The first two specific aims of this proposal describe the creation and characterization of novel folding and assembling molecular systems that in water exploit the stabilizing and recognition abilities of the electron rich 1,5-dialkoxynaphthalene (DAN) and the electron deficient 1,4,5,8-naphthalene tetracarboxylic diimide (NDI) aromatic moieties.最后三个特定目标采取下一个关键步骤，并与生物分子进行不同的相互作用策略。 Spanning the range from basic science to practical application, we will 1) investigate an entirely new aedamer folding topology analogous to nucleic acid hairpins, 2) use the recognition ability of the DAN-NDI interaction to produce large molecular assemblies from smaller folding pieces, 3) investigate the utility of DAN-NDI interactions as a stabilizing force in a protein hydrophobic core, 4) create next-generation threading DNA poly-intercalators based关于我们基于NDI的低聚物NMR分析的结构，以及5）使用噬菌体显示器分离具有高亲和力和特异性的肽，以结合NDI残基链，以在生物医学和生物技术应用中潜在使用。